Core A provides Project researchers with state-of-the-art analytical tools, techniques and experience in the characterization and quantitation of chemical substances and modifications of cellular molecules such as DNA, RNA, lipids, proteins and small-molecule metabolites. It also provides well-characterized cell lines and controlled delivery of nitric-oxide-related DNA and protein damaging agents to these cells to insure quality-control and reproducibility among the Projects. It operates as a service, a developmental laboratory, and as a resource for the Program. Individual researchers use the facilities as needed at three levels: as a service lab, for supervised analyses, or as fully trained users. In addition, we continually expand and improve our capabilities with the development and acquisition of technologies that facilitate the research programs. Specific aims evolve yearly and typically include the development and improvement of Project-related analytical methods, evaluation of new hardware, and evaluation of recently-acquired or potentially useful software. For the year just ending, these were the development and improvement of project-related analytical methods (e.g., quantitation of modified tyrosines), exploitation evaluation of new hardware, and continued focus on targeted quantitation of peptides and proteins, e.g., using click-chemistry-based derivatization for sample enrichment. New equipment and expertise needs are identified in member surveys conducted by the Administrative Core and one-on-one discussions with Project leaders, and via Program- Project group meetings.